Microsurgical and endovascular treatment of un-ruptured cerebral aneurysms by European hybrid neurosurgeons to balance surgical skills and medical staff management.

BACKGROUND: In Europe, aneurysm treatment performed by dually trained neurosurgeons is extremely scarce. We provide outcome data for un-ruptured aneurysm patients treated at a European hybrid center to prove that hybrid neurosurgeons achieve clinical and angiographical results allowing to integrate hybrid neurosurgery into routine aneurysm treatment. This will not only help to maintain neurovascular microsurgical skills but will influence staff costs in related hospitals. METHODS: We retrospectively analyzed all consecutively treated un-ruptured aneurysm patients between 2000 and 2016. The decision-making took into account the pros and cons of both modalities and considered patient and aneurysm characteristics. Clinical outcome was assessed by the modified Rankin scale (mRS). Occlusion rates were stratified into grade I for 100%, grade II for 99-90%, and grade III for <90% occlusion. To account for the introduction of stents, two treatment periods (p1, 2000 to 2008; p2, 2009 to 2016) were defined. RESULTS: The study population consisted of 274 patients (median age 55 years) harboring 338 un-ruptured aneurysms. Microsurgery (MS) was performed in 51.8% and endovascular therapy (EVT) in 43.1%; 5.1% required combined treatment. Overall, 93% showed a favorable clinical outcome (mRS 0-2), 94.3% after MS and 91.5% after EVT. Grade I aneurysm occlusion was achieved in 82.6% patients, 91.9% after MS and 72.9% after EVT. Procedure-related complications occurred after MS in 5.6% and after EVT in 4.4% patients. Mortality was recorded for five (1.8%) patients, one patient after MS and four after EVT. For the EVT cohort, significant improvement from p1 to p2 was seen with clinical outcomes (P=0.030, RR = 0.905, CI: 0.8351-0.9802) and occlusion rates (P=0.039, RR = 0.6790, CI: 0.499-0.923). CONCLUSION: Hybrid neurosurgeons achieve qualified clinical and angiographic results. Dual training will allow to maintain neurovascular caseloads and preserve future aneurysm treatment within neurosurgery. Furthermore economic benefits could be observed in hospital management.

Follow-up after carotid stenting with the CASPER stent system: A duplex ultrasound evaluation.

OBJECTIVE: To report results of duplex ultrasound evaluation of consecutive patients after carotid stenting with the double layer Carotid Artery Stent designed to Prevent Embolic Release (CASPER) stent system. METHODS: Between January 2014 and June 2017, a single-center, retrospective study of 101 consecutive patients (21.8% female; median age, 72.1 years) was performed. Patients with internal carotid artery stenosis treated with the CASPER stent were included. Eligibility criteria for stenting included stenosis of ≥70% of the vessel diameter (or ≥50% diameter with ulceration) in symptomatic carotid artery stenosis or ≥80% stenosis in asymptomatic patients at the carotid artery bifurcation or the proximal cervical internal carotid artery. Duplex ultrasound examination was performed before and within 24 hours of implantation as well as at 14 days, and 3, 6, and 12 months. RESULTS: At the 12-month follow-up visit, moderate in-stent restenosis (ISR) (≥50% and <70%) was detected in three stents (2.8%) and severe (≥70%) ISR in two (1.9%; including one case of stent occlusion). All but the two latter patients remained asymptomatic during the follow-up period. One patient required retreatment for ISR after a minor stroke and another patient with stent occlusion also re-presented with a minor stroke. Multivariable logistic regression was unable to detect any significant factors associated with ISR. CONCLUSIONS: Duplex ultrasound examination after carotid stenting is a useful tool for patient follow-up and determination of ISR. We found a low incidence of ISR assessed by duplex ultrasound examination at 12 months after CASPER stenting, but further studies are warranted.

Severe Leukoaraiosis Is Associated with Poor Outcome after Successful Recanalization of M1 Middle Cerebral Artery Occlusion Strokes.

BACKGROUND: Severe leukoaraiosis (LA) is an established risk factor for poor outcome after mechanical thrombectomy (MT) for large vessel occlusion stroke. There is uncertainty whether this association also applies to successfully recanalized patients with M1 segment middle cerebral artery (MCA) occlusions. METHODS: A retrospective single-centre study of patients with successful reperfusion (thrombolysis in cerebral infarction, TICI 2b or 3) after MT for an M1 MCA occlusion was performed over a 7-year period. LA score (LAS) was assessed using the age-related white matter change scale on pre-interventional brain imaging. RESULTS: A total of 209 patients (median age 75.0 years) were included. LAS was assessed on pre-interventional imaging by computed tomography in 177 (84.7%) patients and magnetic resonance imaging in 32 (15.3%) patients. The median LAS was 1 (IQR 0-8), and severe LA consisted of the top 25 percentile, ranging from 9 to 24. Multivariable analysis demonstrated an association of severe LA (OR 0.32, 95% CI 0.12-0.88, p = 0.023), higher NIHSS on admission (OR 0.89, 95% CI 0.84-0.94, p < 0.001), advanced age (OR 0.97, 95% CI 0.95-1.00, p = 0.039), good leptomeningeal collaterals (OR 3.65, 95% CI 1.46-8.15, p = 0.001), and TICI 3 score (OR 3.26, 95% CI 10.52-7.01) with good clinical outcome after 3 months as measured with the modified Rankin scale. CONCLUSION: Severe LA is associated with poor clinical outcome at 3 months in acute stroke patients undergoing MT due to emergent M1 MCA occlusion.

Carotid Calcium Volume and Stenosis after Stent Implantation.

INTRODUCTION: Internal carotid artery (ICA) stenosis could be treated with stent placement. It was hypothesized that calcium amount could be predictive of vessel stenosis after stent placement. We utilised computed tomography (CT) angiography to quantify volume of calcium material in bulbar ICA. MATERIALS AND METHODS: 28 patients with 31 treated ICA stenosis were collected and analysed using CT angiography-based calcium volume measurement. The Casper stent system (CSS) was used exclusively. Prospective data on emergent carotid stenosis were collected using serial ultrasound controls over a 12-month period. RESULTS: Median age was 76 years (interquartile range (IQR) 67.5-77.8) and the majority were men (71.4%). Plaque median calcium volume was 0.142 cm3 (IQR 0.030 - 0.227) and median average Hounsfield Units (HU) were 561.0 (414.5-675.0). We detected positive linear relationship between average HU and ICA calcium volume. Furthermore, weak positive correlation was observed between calcium volume and residual stenosis as seen on post-interventional angiography, (correlation coefficient R = 0.38, p=0.035). Stronger positive correlation emerged between plaques' average HU and residual stenosis (R = 0.42, p=0.018). Angiographic stenosis showed univariate association with late stenosis as detected 12 months after CAS. CONCLUSION: Calcium burden could be associated with residual stenosis after CSS placement. Larger studies are needed to confirm our preliminary data.

Cerebrovascular manifestations of herpes simplex virus infection of the central nervous system: a systematic review.

BACKGROUND: Intracerebral hemorrhage and ischemic stroke are increasingly recognized complications of central nervous system (CNS) infection by herpes simplex virus (HSV). AIM OF THE STUDY: To analyze clinical, imaging, and laboratory findings and outcomes of cerebrovascular manifestations of HSV infection. METHODS: Systematic literature review from January 2000 to July 2018. RESULTS: We identified 38 patients (median age 45 years, range 1-73) comprising 27 cases of intracerebral hemorrhage, 10 of ischemic stroke, and 1 with cerebral venous sinus thrombosis. Intracerebral hemorrhage was predominantly (89%) a complication of HSV encephalitis located in the temporal lobe. Hematoma was present on the first brain imaging in 32%, and hematoma evacuation was performed in 30% of these cases. Infarction was frequently multifocal, and at times preceded by hemorrhage (20%). Both a stroke-like presentation and presence of HSV encephalitis in a typical location were rare (25% and 10%, respectively). There was evidence of cerebral vasculitis in 63%, which was exclusively located in large-sized vessels. Overall mortality was 21% for hemorrhage and 0% for infarction. HSV-1 was a major cause of hemorrhagic complications, whereas HSV-2 was the most prevalent agent in the ischemic manifestations. CONCLUSION: We found a distinct pathogenesis, cause, and outcome for HSV-related cerebral hemorrhage and infarction. Vessel disruption within a temporal lobe lesion caused by HSV-1 is the presumed mechanism for hemorrhage, which may potentially have a fatal outcome. Brain ischemia is mostly related to multifocal cerebral large vessel vasculitis associated with HSV-2, where the outcome is more favorable.

Neutrophil to lymphocyte ratio predicts intracranial hemorrhage after endovascular thrombectomy in acute ischemic stroke.

BACKGROUND: The development of intracranial hemorrhage (ICH) in acute ischemic stroke is associated with a higher neutrophil to lymphocyte ratio (NLR) in peripheral blood. Here, we studied whether the predictive value of NLR at admission also translates into the occurrence of hemorrhagic complications and poor functional outcome after endovascular treatment (EVT). METHODS: We performed a retrospective analysis of consecutive patients with anterior circulation ischemic stroke who underwent EVT at a tertiary care center from 2012 to 2016. Follow-up scans were examined for non-procedural ICH and scored according to the Heidelberg Bleeding Classification. Demographic, clinical, and laboratory data were correlated with the occurrence of non-procedural ICH. RESULTS: We identified 187 patients with a median age of 74 years (interquartile range [IQR] 60-81) and a median baseline National Institutes of Health Stroke scale (NIHSS) score of 18 (IQR 13-22). A bridging therapy with recombinant tissue-plasminogen activator (rt-PA) was performed in 133 (71%). Of the 31 patients with non-procedural ICH (16.6%), 13 (41.9%) were symptomatic. Patients with ICH more commonly had a worse outcome at 3 months (p = 0.049), and were characterized by a lower body mass index, more frequent presence of tandem occlusions, higher NLR, larger intracranial thrombus, and prolonged rt-PA and groin puncture times. In a multivariate analysis, higher admission NLR was independently associated with ICH (OR 1.09 per unit increase, 95% CI (1.00-1.20, p = 0.040). The optimal cutoff value of NLR that best distinguished the development of ICH was 3.89. CONCLUSIONS: NLR is an independent predictor for the development of ICH after EVT. Further studies are needed to investigate the role of the immune system in hemorrhagic complications following EVT, and confirm the value of NLR as a potential biomarker.

Autoimmune Encephalitis at the Neurological Intensive Care Unit: Etiologies, Reasons for Admission and Survival.

BACKGROUND: Early recognition and treatment of autoimmune encephalitis (AE) has become an essential issue in clinical practice. However, little is known about patients with deteriorating conditions and the need for intensive care treatment. Here, we aimed to characterize underlying aetiologies, clinical symptoms, reasons for intensive care admission, and mortality of critically ill patients with AE. METHODS: We conducted a retrospective chart review of all patients with "definite" or "probable" diagnoses of AE treated at our neurological intensive care unit between 2002 and 2015. We collected and analyzed clinical, paraclinical, laboratory findings and assessed the mortality at last follow-up based on patient records. RESULTS: Twenty-seven patients [median age 55 years (range 25-87), male = 16] were included. Thirteen (48%) had "definite" AE. The most common reasons for admission were status epilepticus (7/27, 26%) and delirium (4/27, 15%). One-year survival was 82%, all five deceased were male, and 3 (60%) of them had "probable" disease. The non-survivors (median follow-up 1 year) were more likely to have underlying cancer and higher need for respiratory support compared to the survivors (p < 0.041, and p = 0.004, respectively). CONCLUSIONS: Clinical presentations and outcomes in critically ill patients with AE are diverse, and the most common leading cause for intensive care unit admission was status epilepticus. The association of comorbid malignancy and the need for mechanical ventilation with mortality deserves further attention.

Fibrinogen consumption is related to intracranial clot burden in acute ischemic stroke: a retrospective hyperdense artery study.

BACKGROUND: Understanding the underlying mechanism of thrombus formation and its components is critical for effective prevention and treatment of ischemic stroke. The generation of thrombotic clots requires conversion of soluble fibrinogen to an insoluble fibrin network. Quantitative features of intracranial clots causing acute ischemic stroke can be studied on non-contrast enhanced CT (NECT). Here, we evaluated on-admission fibrinogen and clot burden in relation to stroke severity, final infarct volume and in-hospital mortality. METHODS: We included 132 consecutive patients with ischemic stroke and presence of hyperdense artery sign admitted within 6 h from symptom onset. Radiological parameters including clot area (corresponding to clot burden) and final infarct volume were manually determined on NECT. National Institute of Health Stroke Scale (NIHSS) was used to quantify disease severity and short-term outcome. RESULTS: Median patient age was 77, 58 % were women, and 63 % had an occlusion of the proximal middle cerebral artery segment. Thrombolysis was performed in 60 % and thrombectomy in 44 %. We identified several independent associations. Higher fibrinogen levels on admission were associated with smaller clot burden (p = 0.033) and lower NIHSS on admission (p = 0.022). Patients with lower fibrinogen had a higher clot burden (p = 0.028) and greater final infarct volume (p = 0.003). Higher fibrinogen was associated with a lower risk of in-hospital death or NIHSS score >15 if discharged alive (p = 0.028). CONCLUSIONS: Our study suggests that intracranial clot burden in acute ischemic stroke is associated with fibrinogen consumption, and shows a complex relationship with disease severity, infarct size and in-hospital survival.

Antiplatelet Usage Impacts Clot Density in Acute Anterior Circulation Ischemic Stroke.

We explored whether clot density in middle cerebral artery (MCA) occlusion is related to clinical variables, stroke etiology, blood constituents, and prestroke medication. We performed a retrospective chart review of patients with acute ischemic stroke of the anterior circulation admitted to two Central European stroke centers. The acquisition of non-contrast enhanced CT (NECT) and CT angiography (CTA) within 4.5 h of symptom onset was obligatory. We assessed the site of MCA occlusion as well as density, area, and length of the clot in 150 patients. The Hounsfield unit values for the clot were divided with contralateral MCA segment to yield relative Hounsfield Unit ratio (rHU). The site of the vessel occlusion (M1 vs. M2) and antiplatelet usage, but not stroke etiology, significantly influenced rHU. We found an inverse correlation of rHU with erythrocyte count (p < 0.001). The multivariate analysis revealed that a higher rHU (i.e., clot being more hyperdense) was more likely with the use of antiplatelets (OR 4.24, CI 1.10-16.31, p = 0.036). Erythrocyte (OR 0.18, CI 0.05-0.55, p = 0.003), and thrombocyte counts (OR 0.99, CI 0.98-0.99, p = 0.029) were associated with odds for more hypodense clots (lower rHU). Our study disclosed that antiplatelet therapy impacts the composition of intracranial clots of the anterior circulation.

Intracranial Thrombus Morphology and Composition Undergoes Time-Dependent Changes in Acute Ischemic Stroke: A CT Densitometry Study.

The aim of our study was to assess whether cerebral artery clots undergo time-dependent morphological and compositional changes in acute ischemic stroke. We performed a retrospective chart review of patients admitted within 5 h from symptom onset to three European stroke centers and evaluated non-contrast-enhanced CT (NECT) for hyperdense artery signs (HAS) in 2565 scans. The occlusion site, density of HAS expressed in Hounsfield units (HU), area of HAS, and relative density (rHU) (HU clot/HU non-affected artery) were studied and related to time from symptom onset, clinical severity, stroke etiology, and laboratory parameters. A HAS was present in the middle cerebral artery (MCA) in 185 (7.2%) and further explored. The mean time from symptom onset to CT was 100 min (range 17-300). We found a time-dependent loss of density in the occluded M1 segment within the first 5 h (N = 118, 95% CI [-15, -2], p = 0.01). Further, the thrombus area in the M2 segment decreased with time (cubic trend N = 67, 95% CI [-63, -8], p = 0.02). Overall, and especially in the M2 segment, a lower clot area was associated with higher fibrinogen (-21.7%, 95% CI [-34.8, -5.8], p = 0.009). In conclusion, our results disclosed time-dependent changes of intracranial thrombi with regard to occlusion site, density and area.

Are arterial calcifications a marker of remodeling in vertebrobasilar territory?

BACKGROUND AND PURPOSE: Intracranial atherosclerosis is responsible for a substantial proportion of stroke, and vessel calcifications as seen on native computed tomographic scans could be an estimate of its burden. The presence of vertebrobasilar artery calcifications is associated with risk factors. METHODS: This study is a retrospective clinical study on 449 consecutive patients with stroke. Native computed tomographic scans were assessed for the presence of calcification in the intracranial segment of vertebrobasilar artery, and the area of each vessel was calculated from 2 perpendicular diameters. A comprehensive assessment of standard risk factors was recorded. RESULTS: A total of 245 (54.6%) patients had visible calcifications in vertebrobasilar artery. Calcifications were positively associated with advanced age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06; P<0.001), larger total vessel area (odds ratio, 1.01; 95% confidence interval, 1.00-1.01; P<0.001), and history of previous transient ischemic attack/stroke (odds ratio, 1.82; 95% confidence interval, 1.08-3.07; P=0.024). CONCLUSIONS: Higher prevalence of calcifications in vertebrobasilar artery territory of patients with stroke is associated with advanced age, larger arterial area, and history of previous transient ischemic attack/stroke.

Thrombus migration in emergent M1 middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: Thrombus migration (TM) is a well-established phenomenon in patients with intracranial vessel occlusion, particularly in those who receive alteplase. However, the relationship between TM, reperfusion success, and clinic-radiological outcomes is still being determined. This study aimed to describe the various outcomes in the event of TM in patients with M1 middle cerebral artery (M1 MCA) occlusion. MATERIALS AND METHODS: The study involved a retrospective analysis of patients undergoing endovascular thrombectomy (EVT) due to M1 MCA occlusion from two tertiary centers between January 2015 and December 2020. The proximal positions of thrombi were measured using a curve tool on CT or MR angiography before EVT. Subsequently, measurements were taken on angiographic imaging. Patients were grouped based on the amount of difference between the two measurements: growth (≤ - 10 mm), stability (> -10 mm and ≤ 10 mm), migration (> 10 mm), and resolution. RESULTS: A total of 463 patients (266 [57%] females, median 76 [interquartile range IQR: 65-83] years) were analyzed. Of them, 106 (22.8%) expressed any degree of TM. In multivariate ordinal regression analysis, the alteplase was significantly associated with TM (t = 2.192, p = 0.028), as was the greater interval from first imaging to angiography (t = 2.574, p = 0.010). In multivariate logistical regression analysis, the good clinical outcome measured by the modified Rankin scale (0-2) was not associated with TM status. CONCLUSIONS: Thrombus migration within the M1 MCA segment occurs in almost a quarter of patients, is associated with alteplase administration, and is mainly irrelevant to radiological and clinical outcome.

Predictors of In-Hospital Mortality after Thrombectomy in Anterior Circulation Large Vessel Occlusion: A Retrospective, Machine Learning Study.

BACKGROUND: Despite the increased use of mechanical thrombectomy (MT) in recent years, there remains a lack of research on in-hospital mortality rates following the procedure, the primary factors influencing these rates, and the potential for predicting them. This study aimed to utilize interpretable machine learning (ML) to help clarify these uncertainties. METHODS: This retrospective study involved patients with anterior circulation large vessel occlusion (LVO)-related ischemic stroke who underwent MT. The patient division was made into two groups: (I) the in-hospital death group, referred to as miserable outcome, and (II) the in-hospital survival group, or favorable outcome. Python 3.10.9 was utilized to develop the machine learning models, which consisted of two types based on input features: (I) the Pre-MT model, incorporating baseline features, and (II) the Post-MT model, which included both baseline and MT-related features. After a feature selection process, the models were trained, internally evaluated, and tested, after which interpretation frameworks were employed to clarify the decision-making processes. RESULTS: This study included 602 patients with a median age of 76 years (interquartile range (IQR) 65-83), out of which 54% (n = 328) were female, and 22% (n = 133) had miserable outcomes. Selected baseline features were age, baseline National Institutes of Health Stroke Scale (NIHSS) value, neutrophil-to-lymphocyte ratio (NLR), international normalized ratio (INR), the type of the affected vessel ('Vessel type'), peripheral arterial disease (PAD), baseline glycemia, and premorbid modified Rankin scale (pre-mRS). The highest odds ratio of 4.504 was observed with the presence of peripheral arterial disease (95% confidence interval (CI), 2.120-9.569). The Pre-MT model achieved an area under the curve (AUC) value of around 79% utilizing these features, and the interpretable framework discovered the baseline NIHSS value as the most influential factor. In the second data set, selected features were the same, excluding pre-mRS and including puncture-to-procedure-end time (PET) and onset-to-puncture time (OPT). The AUC value of the Post-MT model was around 84% with age being the highest-ranked feature. CONCLUSIONS: This study demonstrates the moderate to strong effectiveness of interpretable machine learning models in predicting in-hospital mortality following mechanical thrombectomy for ischemic stroke, with AUCs of 0.792 for the Pre-MT model and 0.837 for the Post-MT model. Key predictors included patient age, baseline NIHSS, NLR, INR, occluded vessel type, PAD, baseline glycemia, pre-mRS, PET, and OPT. These findings provide valuable insights into risk factors and could improve post-procedural patient management.

Effect of concomitant usage of alteplase and mechanical thrombectomy for M1 middle cerebral artery occlusion on clinical outcome: a retrospective analysis of 457 patients from two centers.

Introduction: Endovascular thrombectomy (EVT) and concomitant usage of intravenous alteplase (alteplase) in large vessel occlusion stroke may produce unwanted excess intracerebral hemorrhage (ICH). Whether this applies specifically to isolated occlusion of the M1 segment of the middle cerebral artery (MCA) is unknown. Methods: A retrospective study from two tertiary thrombectomy centers. ICH was determined according to Heidelberg Bleeding Classification (HBC). Factors associated with the occurrence of ICH in EVT alone vs. EVT with alteplase were evaluated using logistic regression analysis. Factors related to the clinical outcome as determined with a modified Rankin scale (mRS) were investigated with univariate and adjusted multivariate logistic regression analysis. The interaction between clinical variables and the usage of alteplase on the occurrence of ICH was evaluated. Results: Any ICH occurred in 156/457 (34.1%) patients Class 1a bleeding in 37 (8.1%), type 2 in 45 (9.8%) Class 1c in 22 (4.8%), Class 2 in 25 (5.5%), and Class 3 (extraparenchymal) in 27 (5.9%). ICH occurred in similar frequency between alteplase-treated patients vs. EVT alone (85/262 [32%] vs. 71/195 [36%]; OR 1.19 (95% CI 0.81-1.76). After adjustment, odds for clinical outcome were lower in ICH patients (OR 0.44 [95% CI 0.25-0.74]), p = 0.002). Higher ICH rate was associated with more EVT steps (p for interaction -0.005), and usage of only stent-retriever (p for interaction =0.005). Conclusion: Utilization of alteplase alongside EVT for MCA M1 occlusion did not result in excessive ICH occurrences or clinical deterioration.

Distance to thrombus, ischemic lesion volume and clinical outcome after thrombectomy for M1 middle cerebral artery occlusion.

BACKGROUND: Stroke resulting from occlusion of the middle cerebral artery (MCA) can have devastating consequences, potentially leading to a loss of independence. This study aimed to investigate the relationship between the distance to the thrombus (DT) and both ischemic lesion volume (ILV) and clinical outcomes. METHODS: We retrospectively evaluated patients with thromboembolic MCA M1 segment occlusion who underwent neurovascular imaging followed by endovascular thrombectomy (EVT) at two comprehensive stroke centers over a 3-year period (2018-2020). Preinterventional computed tomography (CT) or magnetic resonance (MR) angiography was used to measure DT, defined as the distance from the carotid­T bifurcation to the proximal surface of the M1 occlusion. Postinterventional CT or MR imaging was employed to determine the ILV and clinical outcomes were assessed using the modified Rankin scale (mRS) at 3 months. RESULTS: There were 346 patients evaluated. The median DT was 9.4 mm (interquartile range, IQR 6.0-13.7 mm) and the median ILV was 13.9 ml (IQR 2.2-53.1 ml). After adjustment, an increase in DT was associated with a decrease in odds for a larger ILV (odds ratio, OR 0.96, 95% confidence interval, CI 0.92-0.99, p = 0.041). Through this association, more distal thrombi were associated with good clinical outcome (mRS 0-2; clinical outcome available in 282 patients, p = 0.018). The ILV was inversely associated with better clinical outcome OR 0.52 (95% CI 0.40-0.67). CONCLUSION: Based on the findings, DT was identified as an independent albeit weak predictor for ILV and clinical outcomes in patients with MCA M1 occlusion who underwent EVT.

Iatrogenic cerebral amyloid angiopathy: A multinational case series and individual patient data analysis of the literature.

BACKGROUND: The transmission of amyloid ß (Aß) in humans leading to iatrogenic cerebral amyloid angiopathy (iCAA) is a novel concept with analogies to prion diseases. However, the number of published cases is low, and larger international studies are missing. AIMS: We aimed to build a large multinational collaboration on iCAA to better understand the clinical spectrum of affected patients. METHODS: We collected clinical data on patients with iCAA from Austria, Croatia, Italy, Slovenia, and Spain. Patients were included if they met the proposed Queen Square diagnostic criteria (QSC) for iCAA. In addition, we pooled data on disease onset, latency, and cerebrospinal fluid (CSF) biomarkers from previously published iCAA cases based on a systematic literature review. RESULTS: Twenty-seven patients (22% women) were included in this study. Of these, 19 (70%) met the criteria for probable and 8 (30%) for possible iCAA. Prior neurosurgical procedures were performed in all patients (93% brain surgery, 7% spinal surgery) at median age of 8 (interquartile range (IQR) = 4-18, range = 0-26 years) years. The median symptom latency was 39 years (IQR = 34-41, range = 28-49). The median age at symptom onset was 49 years (IQR = 43-55, range = 32-70). Twenty-one patients (78%) presented with intracranial hemorrhage and 3 (11%) with seizures. CONCLUSIONS: Our large international case series of patients with iCAA confirms a wide age boundary for the diagnosis of iCAA. Dissemination of awareness of this rare condition will help to identify more affected patients.

Statin therapy and outcome after ischemic stroke: systematic review and meta-analysis of observational studies and randomized trials.

BACKGROUND AND PURPOSE: Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke. METHODS: The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (≤ 72 hours after stroke), and (2) thrombolysis-treated patients. RESULTS: The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29-1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9-1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62-0.82; P<0.001) and 1 year (OR, 0.80; 95% CI, 0.67-0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0-2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02-1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90-1.44; 4012 patients). CONCLUSIONS: In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed.

Higher on-admission serum triglycerides predict less severe disability and lower all-cause mortality after acute ischemic stroke.

BACKGROUND: High(er) on-admission triglyceride (TG) levels have been suggested as an independent predictor of better outcomes of the acute ischemic stroke. Data regarding poststroke physical disabilities have been contradictory. We aimed to investigate the relationship between fasting on-admission TG and development of disability and all-cause mortality over a 2.5-year period. METHODS: This prospective observational study included 83 acute ischemic stroke patients (29 cardioembolic; 41% men; median age 76 years) followed-up for 28 to 30 months and assessed for physical disability using the Modified Rankin scale (mRS) at 1 week and 3, 12, and 24 months poststroke. TGs were considered as a continuous and a binary variable (≤ 1.27 [n = 43] and >1.27 mmol/L [n = 43]). RESULTS: Higher TGs (continuous or binary) were independently (default adjustments: stroke type, severity at presentation, age, atrial fibrillation, preindex event antiplatelet use, infarct volume, postindex event antiplatelet, statin and angiotensin-converting enzyme inhibitor use, on-admission fasting cholesterol, mean platelet volume, and glomerular filtration rate) were associated with: (1) higher odds of mRS 0 to 2 (none/mild disability) across the assessments (overall odds ratio [OR] 2.73 [95% confidence interval {CI} 1.15-6.38] and OR 3.57 [95% CI 1.04-12.3], respectively); (2) lower odds of mRS worsening between any 2 consecutive assessments (overall OR 0.44 [95% CI 0.20-0.96] and OR 0.35 [95% CI 0.16-0.77], respectively); (3) lower risk of all-cause mortality (hazard ratio 0.47 [95% CI 0.23-0.96] and hazard ratio 0.45 [95% CI 0.21-0.98], respectively). CONCLUSIONS: These data suggest that higher fasting TGs on-admission predict less severe disability, reduced disability progression, and all-cause mortality in patients with acute ischemic stroke.